We conducted this study to identify genetic variants in cancer-related pathway genes which can predict prognosis of NSCLC patients after surgery, using a comprehensive list of regulatory single nucleotide polymorphisms (SNPs) prioritized by RegulomeDB.
A total of 509 potentially functional SNPs in cancer-related pathway genes selected from RegulomeDB were evaluated. These SNPs were analyzed in a discovery set (n = 354), and a replication study was performed in an independent set (n = 772). The association of the SNPs with overall survival (OS) and disease-free survival (DFS) were analyzed.
In the discovery set, 76 SNPs were significantly associated with OS or DFS. Among the 76 SNPs, the association was consistently observed for 5 SNPs (ERCC1 rs2298881C>A, BRCA2 rs3092989G>A, NELFE rs440454C>T, PPP2R4 rs2541164G>A, and LTBP4 rs3786527G>A) in the validation set. In combined analysis, ERCC1 rs2298881C>A, BRCA2 rs3092989, NELFE rs440454C>T, and PPP2R4 rs2541164G>A were significantly associated with OS and DFS (adjusted HR aHR for OS = 1.46, 0.62, 078, and 0.76, respectively; P = 0.003, 0.002, 0.007, and 0.003 respectively; and aHR for DFS = 1.27, 0.69, 0.86, and 0.82, respectively; P = 0.02, 0.002, 0.03, and 0.008, respectively). The LTBP4 rs3786527G>A was significantly associated with better OS (aHR = 0.75; P = 0.003).
Our results suggest that five SNPs in the cancer-related pathway genes may be useful for the prediction of the prognosis in patients with surgically resected NSCLC.
Clinical trial identification
Legal entity responsible for the study
Jae Yong Park
All authors have declared no conflicts of interest.